GM1 ganglioside and Alzheimer's disease

Assembly and deposition of amyloid -protein (A) is an invariable and fundamental event in the pathological process of Alzheimer's disease (AD). To decipher the AD pathogenesis and also to develop disease-modifying drugs for AD, clarification of the molecular mechanism underlying the A assembly into amyloid fibrils in the brain has been a crucial issue. GM1-ganglioside-bound A (GA), with unique molecular characteristics such as having an altered conformation and the capability to accelerate A assembly, was discovered in an autopsied brain showing early pathological changes of AD in 1995. On the basis of these findings, it was hypothesized that GA is an endogenous seed for amyloid fibril formation in the AD brain. A body of evidence that supports this GA hypothesis has been growing over this past 20 years. In this article, seminal GA studies that have been carried out to date, including recent ones using unique animal models, are reviewed.